Compounds and compositions for delivering active agents

ABSTRACT

Carrier compounds and compositions therewith which are useful in the delivery of active agents are provided. Methods of administration and preparation are provided as well.

FIELD OF THE INVENTION

[0001] The present invention relates to compounds for delivering activeagents, and particularly biologically or chemically active agents. Thesecompounds are used as carriers to facilitate the delivery of a cargo toa target. The carrier compounds are well suited to form non-covalentmixtures with biologically-active agents for oral administration toanimals. Methods for the preparation administration of such compositionsare also disclosed.

BACKGROUND OF THE INVENTION

[0002] Conventional means for delivering active agents are oftenseverely limited by biological, chemical, and physical barriers.Typically, these barriers are imposed by the environment through whichdelivery occurs, the environment of the target for delivery, or thetarget itself. Biologically or chemically active agents are particularlyvulnerable to such barriers.

[0003] For example in the delivery to animals of biologically active orchemically active pharmacological and therapeutic agents, barriers areimposed by the body. Examples of physical barriers are the skin andvarious organ membranes that must be traversed before reaching a target.Chemical barriers include, but are not limited to, pH variations, lipidbi-layers, and degrading enzymes.

[0004] These barriers are of particular significance in the design oforal delivery systems. Oral delivery of many biologically or chemicallyactive agents would be the route of choice for administration to animalsif not for biological, chemical, and physical barriers such as varyingpH in the gastro-intestinal (GI) tract, powerful digestive enzymes, andactive agent impermeable gastrointestinal membranes. Among the numerousagents which are not typically amenable to oral administration arebiologically or chemically active peptides, such as calcitonin andinsulin; polysaccharides, and in particular mucopolysaccharidesincluding, but not limited to, heparin; heparinoids; antibiotics; andother organic substances. These agents are rapidly rendered ineffectiveor are destroyed in the gastro-intestinal tract by acid hydrolysis,enzymes, or the like.

[0005] Earlier methods for orally administering vulnerablepharmacological agents have relied on the co-administration of adjuvants(e.g., resorcinols and non-ionic surfactants such as polyoxyethyleneoleyl ether and n-hexadecylpolyethylene ether) to increase artificiallythe permeability of the intestinal walls, as well as theco-administration of enzymatic inhibitors (e.g., pancreatic trypsininhibitors, diisopropylfluorophosphate (DFF) and trasylol) to inhibitenzymatic degradation.

[0006] Liposomes have also been described as drug delivery systems forinsulin and heparin. See, for example, U.S. Pat. No. 4,239,754; Patel etal. (1976), FEBS Letters, Vol. 62, pg. 60; and Hashimoto et al. (1979),Endocrinology Japan, Vol. 26, pg. 337.

[0007] However, broad spectrum use of such drug delivery systems isprecluded because: (1) the systems require toxic amounts of adjuvants orinhibitors; (2) suitable low molecular weight cargos, i.e. activeagents, are not available; (3) the systems exhibit poor stability andinadequate shelf life; (4) the systems are difficult to manufacture; (5)the systems fail to protect the active agent (cargo); (6) the systemsadversely alter the active agent; or (7) the systems fail to allow orpromote absorption of the active agent.

[0008] More recently, microspheres of artificial polymers of mixed aminoacids (proteinoids) have been used to deliver pharmaceuticals. Forexample, U.S. Pat. No. 4,925,673 describes drug-containing proteinoidmicrosphere carriers as well as methods for their preparation and use.These proteinoid microspheres are useful for the delivery of a number ofactive agents.

[0009] There is still a need in the art for simple, inexpensive deliverysystems which are easily prepared and which can deliver a broad range ofactive agents.

SUMMARY OF THE INVENTION

[0010] Compounds and compositions which are useful in the delivery ofactive agents are provided. These compositions include at least oneactive agent, preferably a biologically or chemically active agent, andat least one of the following compounds 1-193, or salts thereof.

1 6-N-(3,5-dichloro-2-hydroxybenzoyl)aminocaproic acid

2 8(2-aminobenzoylamino)caprylic acid

3 8(2-trifluoromethoxy)benzoylamino caprylic acid

4 N-(2-hydroxybenzoyl)isonipecotic acid

5 4-[4-(2-aminobenzoylamino)phenyl]butyrylhydroxamic acid

6 4-(4-(pentafluorobenzoyl)aminophenyl)butyric acid

7 4-(4-(3-anisoyl)aminophenyl)butyric acid

8 8-(3-anisoyl)aminocaprylic acid

9 4-(4-(phenoxyacetyl)aminophenyl)butyric acid

10 4-(4-(2-nitrobenzenesulfonyl)aminophenyl)butyric acid

11 8-(2-nitrobenzenesulfonyl)aminocaprylic acid

12 6-(4-(salivyloyl)aminophenyl)hexanoic acid

13 8-(2-methoxybenzoyl)amino caprylic acid

14 2-[4-Salicyloylamino)phenyl]ethyl methyl sulfone

15 1-Salicyloyl-2-succinyl hydrazide

16 3-(4-(2,5-dimethoxycinnamoyl)aminophenyl)propionic acid

17 4-(4-(2,5-dimethoxycinnamoyl)aminophenyl)butyric acid

18 1-salicyloyl-2-glutaryl hydrazide

19 Succinyl-4-aminosalicylic acid

20 8-(Phenoxyacetylamino)caprylic acid

21 8-(2-pyrazinecarbonyl)aminocaprylic acid

22 4-(4-(2-pyrazinecarbonyl)aminophenyl)butyric acid

23 6-(4-(N-2-Nitrobenzoyl)aminophenyl)hexanoic acid

24 6-(4-(N-2-aminobenzoyl)aminophenyl)hexanoic acid

25 4-(4-(2-(3-carboxyl)pyrazinecarboxyl)aminophenyl)butyric acid

26 4(2-Nitrobenzoyl)aminophenylsuccinic acid

27 8-(2-(trifluoromethoxy)benzoyl)aminocaprylic acid

28

29 8-(Benzylcarbonylamino)caprylic acid

30 8-(phenylcarbonylamino)caprylic acid

31 2-[4-(2-Methoxybenzoylamino)phenyl]ethyl H₂PO₄

32 1-salicyloyl-2-suberyl hydrazide

33 4-(4-benzyloxycarbonylaminophenyl)butyric acid

34 4-(4-(2-hydroxynicotinoyl)aminophenyl)butyric acid

35 9-Salicyloylaminononanionic acid

36 4-(4-phenyloxycarbonylaminophenyl)butyric acid

37 3-(2-methoxybenzoylamino)-1-propanol

38 8-(2-Hydroxynicotinoyl)aminocaprylic acid

39 6-(2-methoxybenzoyl)amino nicotinic acid

40 salicyloylglycine

41 4-(1-(2-pyrimidyl)piperazinoyl)butyric acid

42 8-(chromone-3-carbonyl)aminocaprylic acid

43 8-(vinylbenzoyl)aminocaprylic acid

44 4-(4-(chromone-3-carbonyl)aminophenyl)butyric acid

45 8-cinnamoylaminocaprylic acid

46 6-(N-salicyloylamino)valeric acid

47 9-(2-hydroxybenzoamido)nonanic acid

48 N-(4-salicyloylamino)-6-caproic acid

49 4′-flavonic acid

50 11-cinnamoylaminoundecanoic acid

51 4-octanoylamino-3-hydroxybenzoic acid

52 (3Phenyl2,3-dihydroxypropanoyl)8aminocaprylic acid

53 8-[N-(3-coumarincarbonyl)]aminocaprylic acid

54 8-[N-(4-chlorobenzoyl)]aminocaprylic acid

55 8-[N-3-fluorobenzoyl)]aminocaprylic acid

56 8-(N-2,5-Dihydroxybenzoyl)amninocaprylic acid

57 8-(N-2,3-Dimethoxybenzoyl)aminocaprylic acid

58 8-(N-2,4-Dihydroxybenzoyl)aminocaprylic acid

59 8-(N-2,5-Dimethoxybenzoyl)aminocaprylic acid

60 8-(N-3,5-Diacetyloxybenzoyl)aminocaprylic acid

61 8-(N-4-Hydroxylbenzoyl)aminocaprylic acid (dimer)

62 8-(N-2,4-Dihydroxybenzoyl)aminocaprylic acid

63 10-(N-2-Methoxyanilino)sebalic acid

64 10(N-2-Methoxyanilino)sebacic acid

65 2-Methoxybenzeneaminodecanoic acid

66 8-(N-benzoyl)aminocaprylic acid

67 8-(N-2-Hydroxy-4-methoxybenzoyl)aminocaprylic acid

68 8-[N-(4-fluorobenzoyl)]aminocaprylic acid

69 8-[N-(3-bromobenzoyl)]aminocaprylic acid

70 8-(4-(1,2-dihydroxyethyl)benzoyl)aminocaprylic acid

71 8-[N-(4-bromobenzoyl)]aminocaprylic acid

72 8-[N-(4-iodobenzoyl)]aminopcaprylic acid

73 4-{4-[N-(2-iodobenzoyl)aminophenyl]}butyric acid

74 4-{4-[N-(1-hydroxy-2-naphthoyl)aminophenyl]}butyric acid

75 4-{4-(2,4-dimethoxylbenzoyl)aminophenyl)butyric acid

76 4-(o-anisoyl)aminophenylacetic acid

77 3-[4-(2,4-dimethoxybenzoyl)aminophenyl]propionic acid

78 4-{4-[N-(4-iodobenzoyl)]aminophenyl}butyric acid

79 3-[4-(2,3-dimethoxybenzoyl)aminophenyl]propionic acid

80 4{4-[N-2-bromobenzoyl)]aminophenyl}butyric acid

81 4{4-[N-3-bromobenzoyl)aminophenyl)}butyric acid

82 8-(N-3,5-Dihydroxybenzoyl)aminocaprylic acid

83 8-(N-3,5-Dimethoxy 4-hydroxybenzoyl)aminocaprylic acid

84 8-(N-2-6-Dimethoxybenzoyl)amino caprylic acid

85 4-{4-[N-(4-bromobenzoyl)aminophenyl]}butyric acid

86 8-(2-hydroxy-4-chlorobenzoyl)aminocaprylic acid

87 8-(N-2,6-Dihydroxybenzoyl)aminocaprylic acid

88 8-(N-2-Hydroxy6-methoxybenzoyl)aminocaprylic acid

89 8-(5-chloro-o-anisoyl)aminocaprylic acid

90 4-(4-(2,3-dimethoxybenzoyl)aminophenyl)butyric acid

91 4-(4-(5-chloro-o-anisoyl)aminophenyl)butyric acid

92 4-(4-(4-chloro-o-anisoyl)aminophenyl)butyric acid

93 8-(4-chloro-o-anisoyl)aminocaprylic acid

94 3-(4-(2,5-dimethoxybenzoyl)aminophenyl)propionic acid

95 4-{N-[4-(3-iodobenzoyl)aminophenyl]}butyric acid

96 7-cinnamoylaminoheptanoic acid

97 8-N-(3-iodobenzoyl)aminocaprylic acid

98 8-N-(4-methoxy-3-nitrobenzoyl)aminocaprylic acid

99 8-N-(2-methoxy-4-nitrobenzoyl)aminocaprylic acid

100 4-{N-[4-(2-methoxy-4-nitrobenzoyl)aminophenyl]}butyric acid

101 4-(4-(2,5-dimethoxybenzoyl)aminophenyl)butyric acid

102 8-(N-2-hydroxy-5-bromobenzoyl)aminocaprylic acid

103 3-Indolebutyric acid

104

105

106

107 4-(4-(2,6-dimthoxybenzoyl)aminophenylbutyric acid

108 4-[4-N-(4-methoxy-3-nitrobenzoyl)aminophenyl]butyric acid

109 8-(N-2-hydroxy-5-chlorobenzoyl)aminocaprylic acid

110 8-(N-2-hydroxy-5-iodobenzoyl)aminocaprylic acid

111 8-(3-hydroxy-2-naphthoyl)aminocaprylic acid

112 8-(N-2-hydroxy-4-nitrobenzoyl)aminocaprylic acid

113 4-[-N-(2-hydroxy-4-bromobenzoyl)aminophenyl]butyric acid

114 8-(N-2,3-Dihydroxybenzoyl)aminocaprylic acid

115 8-(N-3-methylsalicyloyl)aminocaprylic acid

116 8-(N-5-methylsalicyloyl)aminocaprylic acid

117 9-(cinnamoylamino)nonanionic acid

118 4-(4-(2-chloro-5-nitrobenzoyl)aminophenyl)butyric acid

119 4-{-[N-(2-hydroxy-5-iodobenzoyl)]aminophenyl}butyric acid

120 N-2-nitrophenyl-N′-(8-octanoic acid)urea

121 N-(2-methoxy-5-nitrophenyl)sebacoyl amide acid

122 8-[N-(2-acetoxy-3,5-dichlorobenzoyl)]aminocaprylic acid

123 8-[N-(2-acetoxy-3,5-dibromobenzoyl)]aminocaprylic acid

124 8-N-(2-chloro-6-fluorobenzoyl)aminocaprylic acid

125

126 8-N-(4-hydroxy-3-nitrobenzoyl)caprylic acid

127 4-(4-Salicyloylaminophenyl)-4-oxobutyric acid

128 12-cinnamoyldodecanoic acid

129 4-{4-[N-(3-hydroxy-2-naphthoyl)aminophenyl]}butyric acid

130 8-(4-chloro-3-nitrobenzoyl)aminocaprylic acid

131 8-(2-chloronicotinoyl)aminocaprylic acid

132 8-(2-chloro-5-nitrobenzoyl)aminocaprylic acid

133 4-(4-phthalimidophenyl)butyric acid

134 4-{4-[N-(3-hydroxy-2-naphthoyl)aminophenyl]}propanoic acid

135 3-(4-(2,6-dimethoxybenzoyl)aminophenyl)propionic acid

136 8-(N-2-hydroxy-3,5-diiodobenzoyl)aminocaprylic acid

137 8-(N-2-chloro-4-fluorobenzoyl)aminocaprylic acid

138 8-(2-(1,2-dihydroisoindole-1-one)octanoic acid

139 8-(N-1-hydroxy-2-naphthoyl)aminocaprylic acid

140 8-(phthalimido)caprylic acid

141 10(4-chloro-2-hydroxyanilino)sebaic acid monoamide

142 6-(anisoyl)aminocaproic acid

143 4-(4-(4-chloro-3-nitrobenzoyl)aminophenyl)butyric acid

144 11-N-(1-hydroxy-2-naphthoyl)aminoundecanoic acid

145 Bis(N-2carboxylphenyl-N-(N′-8-octanoic acid)ureal)oxalyl diamide

146 2-[2-N-(2-chlorobenzoyl)aminoethoxy]ethanol

147 2-[2-N-(4-chlorobenzoyl)aminoethoxy]ethanol

148 4-(2-methoxybenzoyl)amino 3-carboxysulfoxide

149 4-(2-methoxybenzoyl)amino 3-carboxypropylsulfone

150 4-(4-(3-hydroxyphthalimido)phenyl)butyric acid

151 2-[2-N-(2-methoxybenzoyl)aminoethoxy)]ethanol

152 2-[2-N-(3-chlorobenzoyl)aminoethoxy)]ethanol

153 Bis(N-2-carboxyphenyl-N-(N′-3(4-aminophenyl)propionicacid)ureal)oxalyl diamide

154 trans-4-(2-aminobenzamidomethyl)cyclohexamecarboxylic acid

155 11-N-(3,5-dichloro-2-hydroxybenzoyl)aminoundecanoic acid

156 2-[N-(2-bromobenzoyl)aminoethoxy]ethanol

157 7-N-(3,5-dichloro-2-hydroxybenzoyl)aminoheptanoic acid

158 N-[3,5-dichloro-2-hydroxybenzoyl-4(4-aminophenyl)]butyric acid

159 trans-4-(N-salicyloylaminomethyl)cyclohexane carboxylic acid

160 N-[3,5-dichloro-2-hydroxybenzoyl-3-(4-aminophenyl)]propionic acid

161 12-N-(3,5-dichloro-2-hydroxybenzoyl)aminododecanoic acid

162 N-(2-hydroxy-4-carboxy)-6-heptenamide

163 N-(2-bromobenzoyl)morpholine

164 8-N-cyclohexanoylaminocaprylic acid

165 2-[N-(2-iodobenzoyl)aminoethoxy]ethanol

166 5-(4-chloro-2-hydroxyanilinocarbonyl)valeric acid

167 8-(2-hydroxyphenoxy)-aminocaprylic acid

168 N-Salicyloyl-5-(3-aminophenyl)valeric acid

169 4-(4-(2-ethoxybenzoyl)aminophenyl)butyric acid

170 9-[2-(3-hydroxy)pyridylaminocarbonyl]nonanic acid

171 7-(2-hydroxyphenoxyacetyl)aminocaprylic acid

172 2-[N-(2-hydroxybenzoylamino)ethoxy]ethanol

173 4-[N-(3,5-dichloro-2-hydroxybenzoyl)]aminophenylacetic acid

174 8-(2-hydroxy-5-chloroanilinocarbonyl)octanoic acid

175 N-salicyloyl-5-(4-aminophenyl)valeric acid

176 9-(2-hydroxy-5-methylanilinocarbonyl)nonanoic acid

177 5-(2-hydroxy-5-methylanilinocarbonyl)valeric acid

178 8-(pentafluorobenzoyl)aminocaprylic acid

179 3-(3-(salicyloyl)aminophenyl)propionic acid

180 8-(2-ethoxybenzoyl)aminocaprylic acid

181 4-(4-(2-Diethylaminobenzoic)aminophenyl)butyric acid

182 8-(3-Phenoxy)propionylamino)caprylic acid

183 4-(Salicyloyl)aminophenylethyltetrazole

184 8(-(4(N-Salicyloyl-4aminophenyl)butyric)aminocaprylic acid

185 4-(4-(N-(2-Fluorocinnamoyl))aminophenyl)butyric

186 4-(4-(N-8(N-Salicyloyl)aminocaprylic)aminophenyl)butyric acid

187 8-(p-anisoyl)aminocaprylic acid

188 8-(4-Hydroxybenzoyl)aminocaprylic acid

189 8-(3-Hydroxybenzoyl)aminocaprylic acid

190 8-(3,4,5-Trimethoxybenzoyl)aminocaprylic acid

191 8-(N-4-Methylsalicyloyl)aminocaprillic acid [sic]

192 N-10-(2-hydroxy-5-nitroanilino)decanoic acid

193 4-(4-(2-chloronicotinoyl)aminophenyl)butyric acid

[0011] Compositions comprising the carrier compounds discussed above andactive agents are effective in delivering active agents to selectedbiological systems.

DETAILED DESCRIPTION OF THE INVENTION

[0012] The specific compositions of the present invention include anactive agent and a carrier. These compositions may be used to delivervarious active agents through various biological, chemical, and physicalbarriers and are particularly suited for delivering active agents whichare subject to environmental degradation. The compositions of thesubject invention are particularly useful for delivering oradministering biologically or chemically active agents to any animalssuch as birds including, but not limited to, chickens; mammals, such asprimates and particularly humans; and insects.

[0013] Other advantages of the present invention include the use of easyto prepare, inexpensive raw materials. The compositions and theformulation methods of the present invention are cost effective, simpleto perform, and amenable to industrial scale up for commercialproduction.

[0014] Subcutaneous, sublingual, and intranasal coadministration of anactive agent, such as, for example, recombinant human growth hormone(rhGH); salmon calcitonin; heparin, including, but not limited to, lowmolecular weight heparin; parathyroid hormone; and compounds incompositions as described herein result in an increased bioavailabilityof the active agent compared to administration of the active agentalone.

[0015] Active Agents

[0016] Active agents suitable for use in the present invention includebiologically or chemically active agents, chemically active agents,including, but not limited to, fragrances, as well as other activeagents such as, for example, cosmetics.

[0017] Biologically or chemically active agents include, but are notlimited to, pesticides, pharmacological agents, and therapeutic agents.For example, biologically or chemically active agents suitable for usein the present invention include, but are not limited to, peptides, andparticularly small peptides; hormones, and particularly hormones whichby themselves do not or only a fraction of the administered dose passesthrough the gastro-intestinal mucosa and/or are susceptible to chemicalcleavage by acids and enzymes in the gastro-intestinal tract;polysaccharides, and particularly mixtures of muco-polysaccharides;carbohydrates; lipids; or any combination thereof. Further examplesinclude, but are not limited to, human growth hormones; bovine growthhormones; growth releasing hormones; interferons; interleukin-1;insulin; heparin, and particularly low molecular weightheparin;calcitonin; erythropoietin; atrial natureticfactor; antigens; monoclonalantibodies; somatostatin; adrenocorticotropin, gonadotropin releasinghormone; oxytocin; vasopressin; cromolyn sodium (sodium or disodiumchromoglycate); vancomycin; desferrioxamine (DFO); parathyroid hormoneanti-microbials, including, but not limited to anti-fungal agents; orany combination thereof.

[0018] Carriers

[0019] Although compounds 1-193 above have been found to act as carriersfor the oral delivery of biologically or chemically active agents,special mention is made of compounds 9, 35, 64, 67, 79, 102, 109, 111,117, 122, 136, and 141, above.

[0020] Properties of compounds 1-193 are listed in Table 1, below. TABLE1 Carrier Properties Anal. Calculated For Found Melting Compound C H N SC H N S Point (° C.) 1 48.8 4.70 4.40 48.81 4.64 4.39 2 64.73 7.97 10.0664.54 7.81 10.19 3 55.33 5.80 4.03 55.40 5.79 3.96 69-71 4 62.64 6.065.62 62.75 6.08 5.51 151-154 5 65.16 6.11 13.40 65.29 6.03 13.29 144-1456 54.70 3.24 3.75 54.29 3.24 3.54 165-169 7 69.00 6.11 4.47 69.09 6.244.43 126-129 8 65.51 7.90 4.78 65.60 8.25 4.83 89-90 9 68.99 6.11 4.4769.01 6.08 4.47 104-107 10 52.74 4.42 7.69 52.91 4.45 7.49 142-145 1148.83 5.85 8.14 48.95 5.89 8.02 120-122 12 69.71 6.47 4.28 69.56 6.474.38 144-146 13 65.51 7.90 4.77 65.23 7.88 4.72 72.5-74.5 14 60.17 5.364.39 10.04 60.09 5.36 4.35 9.99 155-156 15 52.38 4.79 11.11 52.45 4.9411.08 220-222 16 67.60 5.95 3.94 67.34 6.01 3.91 219-222 17 68.09 6.533.78 67.77 6.24 3.81 130-133 18 54.13 5.30 10.52 54.12 5.24 10.54192.5-195.5 19 55.26 4.21 7.16 54.48 4.32 6.86 >280 dec 20 65.51 7.904.77 65.52 7.90 4.77 75-80 21 58.85 7.21 15.84 58.86 7.16 15.69 120-12222 63.15 5.30 14.73 63.30 5.43 14.18 197-201 23 64.04 5.66 7.86 64.175.67 7.75 188-190 24 69.91 6.88 8.46 69.98 6.79 8.58 131-134 25 58.364.56 12.76 58.20 4.63 12.61 138-141 26 56.98 3.94 7.82 56.39 3.92 7.74221-223 27 55.33 5.80 4.03 55.47 6.10 4.04 70-72 28 29 65.74 7.58 4.7965.51 7.89 4.78 52-55 30 64.50 7.57 5.02 64.07 7.81 5.40 70-74 31 54.705.17 3.99 54.50 4.99 3.95 173-174 32 58.63 5.94 9.12 58.73 6.20 10.34125-129 33 69.00 6.10 4.47 69.18 6.08 4.54 100-102 34 63.99 5.37 9.3363.46 5.35 9.06   218-221 C. 35 65.5 7.90 4.78 65.37 8.00 4.66   96-97C. 36 68.22 5.72 4.68 67.88 5.65 4.55 134-137 37 63.14 7.23 6.69 63.157.29 6.58 53.5-56   38 60.00 7.14 10.00 59.78 7.31 9.94 135-138 39 61.674.41 10.29 61.69 4.41 10.12 >225    40 55.39 4.65 7.18 55.52 4.77 7.30162.5-166   41 56.10 6.52 20.14 55.66 6.71 19.69 129-131 42 65.24 6.394.23 65.42 6.16 3.78   130-133.5 43 70.59 7.96 4.84 70.35 8.13 4.79111-113 44 68.37 4.88 3.99 68.61 4.89 3.79 120-123 45 70.59 7.96 4.8470.48 7.97 4.71 108-110 46 60.75 6.37 5.90 60.97 6.18 5.80 100.5-103  47 64.50 7.57 5.02 64.42 7.58 5.01  97-100 48 64.86 5.98 7.56 64.50 6.017.52 165-169 49 72.18 3.76 0.00 72.13 3.84 0.00 >225    50 72.51 8.764.23 72.39 8.84 4.12 120-122 51 64.50 7.58 5.01 64.75 7.65 4.69200.5-204   52 7.74 4.33 7.82 4.30 88-89 53 65.24 6.39 4.23 65.15 6.464.23 93-97 54 60.49 6.77 4.70 60.54 6.76 4.65 114-116 55 64.04 7.17 4.9863.90 7.11 4.93 105-106 56 61.00 7.17 4.74 60.49 6.92 4.65 146-148 5763.14 7.79 4.33 63.22 7.82 4.36 59-61 58 63.14 7.79 4.33 63.17 7.86 4.26102-104 59 63.14 7.79 4.33 63.35 7.68 4.20 89-90 60 60.15 6.64 3.6959.84 6.66 3.64 112-113 61 65.53 8.85 6.65 65.34 8.73 6.67 89-92 6261.00 7.17 4.74 60.94 7.12 4.49 104-108 63 66.43 8.20 4.56 66.29 8.234.36 77-78 64 65.51 7.90 4.77 65.52 8.06 4.54 97-98 65 69.59 9.28 4.7769.64 9.35 4.86 62-65 66 68.41 8.04 5.32 68.41 8.06 5.28 88-89 67 62.127.49 4.53 61.94 7.45 4.43 98-99 68 64.04 7.17 4.98 64.07 7.16 4.95106-107 69 52.64 5.89 4.09 52.63 5.85 4.03 109-110 70 63.15 7.74 4.3363.26 7.90 4.14  97-100 71 52.64 5.89 4.09 52.67 5.99 3.97 114-115 7246.31 5.18 3.61 46.25 4.86 3.52 143-144 73 49.89 3.94 3.42 49.92 3.853.39 170-171 74 72.19 5.48 4.01 71.51 5.33 3.75 180 75 66.46 6.16 4.0866.47 6.26 4.06 168.5-171   76 67.37 5.26 4.91 67.31 5.25 5.07 130-13377 65.65 5.78 4.26 65.49 6.04 4.26 179-183 78 49.89 3.94 3.42 49.8 3.713.29 237-238 79 65.65 5.78 4.26 65.21 6.05 4.24 156-158 80 56.38 4.453.87 56.4 4.21 3.91 130-131 81 56.38 4.45 3.87 56.46 4.5 3.84 197-198 8256.6 7.49 4.4 56.3 7.49 4.14 58-62 83 57.03 8.2 3.91 57.17 7.8 3.7138-140 84 57.58 7.11 3.95 57.52 7.7 3.94 85 56.38 4.45 3.87 56.31 4.253.64 230-231 86 57.42 6.42 4.46 57.14 6.45 4.2 116-117 87 61 7.17 4.7461.18 7.05 4.65 108-109 88 62.12 7.49 4.53 62.34 7.21 4.39 107-109 8958.63 6.76 4.27 58.53 6.81 4.2 117-118 90 66.46 6.16 4.08 66.18 6.153.84 100-104 91 62.16 5.21 4.03 61.93 4.97 3.86 183-185 92 62.16 5.214.03 62.2 5.14 3.98 167-170 93 58.63 6.76 4.27 58.64 6.83 4.19 106-10894 65.65 5.81 4.25 65.56 5.64 4.2 153-156 95 49.89 3.94 3.42 49.9 3.813.18 216-217 96 69.82 7.64 5.09 69.91 7.66 5.02 129-131 97 46.31 5.183.61 46.54 4.95 3.64 122-123 98 56.8 6.55 8.28 56.69 6.67 8.1 99 56.86.55 8.28 57.37 6.57 8.33 117:118 100 60.33 5.06 7.82 59.98 4.97 7.67207-209 101 66.46 6.16 4.08 66.37 6.32 3.96 126-128 102 50.29 5.63 3.9150.14 5.7 3.76 129-131 103 70.93 5.95 6.89 70.94 6.44 6.89 104 65.846.14 8.53 65.94 6.19 8.54 228-231 105 64.96 5.77 8.91 64.89 5.82 8.82106 66.65 6.48 8.18 66.39 6.49 8.05 140-142 107 66.47 6.12 4.07 66.56.26 4.08 140-142 108 60.33 5.06 7.82 60.32 4.99 7.78 150-151 109 57.416.42 4.46 57.07 6.44 4.39 121-123 110 44.46 4.97 3.46 133-135 111 69.287.03 4.25 68.86 7.07 4.11 147-149 112 55.55 6.22 8.64 55.27 5.99 8.5120-121 113 53.99 4.26 3.7 53.98 4.25 3.63 210 decom 114 57.49 7.39 4.7457.72 7.57 4.43 80-83 115 65.5 7.9 4.77 64.97 7.79 4.75 90-92 116 65.57.9 4.77 65.11 8.03 4.71 125-127 117 71.26 8.3 4.2 70.6 7.89 4.83 94-96118 56.29 4.17 7.72 56.23 4.01 7.6 173-175 119 47.89 3.81 3.29 47.523.71 3.16 236-237 120 55.7 6.55 13 55.71 6.58 13.05 123-5  121 57.985.81 7.95 57.9 7.11 7.82 131-133 122 51.74 5.5 4.02 51.41 5.43 3.61  118-119.5 123 41.22 4.38 3.2 41.45 4.36 2.94   143-144.5 124 57.066.06 4.44 57.02 6.12 4.35 57-58 125 61.18 4.83 4.2 60.71 4.76 3.89 214decom 126 55.55 6.22 8.64 55.4 6.24 8.53 150-151 127 65.17 4.83 4.4765.27 4.87 4.48 208-209 128 73.03 8.99 4.06 72.92 9.36 4.1  99-101 12972.25 5.44 4 72.14 5.24 4.01 216-217 130 52.56 5.58 8.17 52.66 5.44 8.21 96-100 131 56.28 6.41 9.38 56.32 6.42 9.28  98-100 132 52.56 5.58 8.1752.46 5.65 7.86 150-153 133 69.89 4.89 4.53 69.64 5 4.54 136-9  13471.68 5.2 4.2 71.24 5.1 4.13 251-253 135 65.64 5.78 4.25 65.3 5.91 4.0479-83 136 33.92 3.61 2.64 34.48 3.84 2.48 164-165 137 57.06 6.06 4.4457.09 6.17 4.45 88-89 138 69.79 7.69 5.09 69.68 7.78 5.08 102-3  13969.28 7.04 4.25 68.99 7 4.1 107-108 140 66.42 6.62 4.84 66.2 6.49 4.8188-9  141 58.62 6.76 4.27 58.66 6.93 4.18 134-135 142 63.38 7.21 5.2863.22 7.28 5.24 71-73 143 56.29 4.17 7.72 56.19 4.04 7.65 156-160 14471.13 7.88 3.77 70.39 7.91 3.64 95-97 145 58.44 6.06 8.02 58.25 6.387.84 165-8  146 54.22 5.79 5.75 54.26 5.65 5.69   77-78.5 147 54.22 5.795.75 54.21 5.85 5.61 80-81 148 58.78 4.93 40.3 58.64 4.89 3.97 172-173149 56.19 4.72 3.85 56.31 4.67 3.86 177 150 66.46 4.65 4.31 66.41 4.564.23 158-160 151 58.61 7.24 5.69 58.79 7.35 5.66 152 54.22 5.79 5.7554.21 5.72 5.62 54-55 153 60.85 4.25 7.89 60.27 4.37 7.89 >260    15462.5 7.3 10.14 64.77 7.27 9.9 187-190 155 55.4 6.5 3.6 55.56 6.51 3.5114-116 156 45.85 4.9 4.86 46.06 4.78 4.71 67-68 156 48.8 4.7 4.4 48.814.64 4.39 144-146 157 50.3 5.1 4.2 50.25 5.12 3.99 141-143 158 55.5 4.13.8 55.55 3.88 3.75 190-192 159 64.97 6.9 5.05 64.7 6.82 5.02 171-174160 54.3 3.7 4 54.31 3.58 3.83 222-224 161 56.4 6.7 3.5 56.69 6.98 3.1176-78 162 63.63 6.47 5.3 64.76 6.84 4.74 188-191 163 48.91 4.48 5.1948.89 4.31 5.10 88.5-90   164 66.66 10.04 5.18 66.69 10.77 5.1667.5-70.5 165 39.42 4.21 4.18 39.19 4.35 3.88 oil 166 53.05 5.19 5.1653.06 5.03 4.86 151-152 167 65.53 7.85 4.78 65.4 7.84 4.57 85-89 16868.99 6.11 4.47 68.62 5.87 4.49 162-6  169 69.71 6.47 4.28 69.67 6.584.50 132.5-135   170 61.21 7.53 9.52 61.21 7.68 9.46 134-135 171 62.147.44 4.53 61.96 7.52 4.57 101-104 172 58.63 6.71 6.22 58.15 6.83 6.04173 52.96 3.26 4.12 52.96 3.28 4.02 225-227 174 57.42 6.42 4.46 57.36.38 4.39 119-120 175 68.99 6.11 4.47 68.84 6.08 4.51 131-4  176 66.438.2 4.56 66.42 8.16 4.51 109-110 177 62.14 6.82 5.57 61.96 6.66 5.52127-128 178 51.00 4.56 3.97 51.09 4.61 3.93 179 67.36 5.30 4.90 67.265.24 4.91 185-186 180 66.43 8.20 4.56 66.32 8.60 5.12 51.5-55   18169.92 6.79 8.58 67.02 6.93 8.20 81-84 182 66.46 8.14 4.56 66.43 8.344.47 82-84 183 62.13 4.89 22.64 62.05 4.88 22.45 271-272 184 68.16 7.326.36 67.73 7.44 6.70 114-117 185 71.30 5.98 5.73 71.10 5.97 5.74 146-149186 68.16 7.32 6.36 67.94 7.31 6.41 105-108 187 65.51 7.90 4.77 65.357.63 4.59 102-103 188 64.50 7.58 5.01 64.19 7.69 4.83 133-134 189 64.57.58 5.01 64.5 7.57 4.90 116-118 190 61.15 7.71 3.97 61.27 7.79 4.08124-127 191 65.5 7.9 4.77 65.32 7.94 4.7 114-115 192 56.77 6.51 8.2856.83 6.76 8.21 141-143 193 60.29 4.74 8.79 60.17 4.58 8.74 202-205 19448.8 4.7 4.4 48.81 4.64 4.39 144-146

[0021] These carrier compounds or poly amino acids, and peptides,including the amino acids, may be used to deliver active agentsincluding, but not limited to, biologically or chemically active agentssuch as for example, pharmacological and therapeutic agents.

[0022] An amino acid is any carboxylic acid having at least one freeamine group and includes naturally occurring and synthetic amino acids.

[0023] Poly amino acids are either peptides or two or more amino acidslinked by a bond formed by other groups which can be linked, e.g. anester, anhydride, or an anhydride linkage.

[0024] Peptides are two or more amino acids joined by a peptide bond.Peptides can vary in length from dipeptides with two amino acids to polypeptides with several hundred amino acids. See Chambers BiologicalDictionary, editor Peter M. B. Walker, Cambridge, England: ChambersCambridge, 1989, page 215. Special mention is made of di-peptides,tri-peptides, tetra-peptides, and penta-peptides.

[0025] Salts such as, for example, sodium salt of these carriercompounds can be used as well.

[0026] Many of the compounds described herein are derived from aminoacids.

[0027] Many of the compounds of the present invention can be readilyprepared from amino acids including, but not limited to, aminocaprylicacid, butyrylhydroxaminic acid, aminophenylbutyric acid,aminophenylhexanoic acid, aminophenylpropionic acid, amino salicylicacid, aminophenylsuccinic acid, aminononanic acid, aminonicotinic acid,amino valenic acid, aminophenylacetic acid, aminocaproic acid,aminoundecanoic acid, aminoheptanoic acid, aminohydroxybenzoic acid, andaminodecanoic acid by methods within the skill of those in the art basedupon the present disclosure and the methods described in U.S. patentapplication Ser. No. 60/017,902, filed Mar. 29, 1996; Ser. No.08/414,654, filed Mar. 31, 1995; Ser. No. 08/335,148, filed Oct. 25,1994; and No. 60/003,111, filed Sep. 1, 1995.

[0028] For example, these compounds may be prepared by reacting thesingle acid with the appropriate agent which reacts with free aminomoiety present in the amino acids to form amides. Protecting groups maybe used to avoid unwanted side reactions as would be known to thoseskilled in the art.

[0029] The carrier compound may be purified by recrystallization or byfractionation on solid column supports. Suitable recrystallizationsolvent systems include acetonitrile, methanol and tetrahydrofuran.Fractionation may be performed on a suitable solid column supports suchas alumina, using methanol/n-propanol mixtures as the mobile phase;reverse phase column supports using trifluoroacetic acid/acetonitrilemixtures as the mobile phase; and ion exchange chromatography usingwater as the mobile phase. When anion exchange chromatography isperformed, preferably a subsequent 0-500 mM sodium chloride gradient isemployed.

[0030] Delivery Systems

[0031] The compositions of the present invention may include one or moreactive agents.

[0032] In one embodiment, compounds or salts of compounds 1-193 or polyamino acids or peptides that include at least one of these compounds orsalts may be used directly as a delivery carrier by simply mixing one ormore compound or salt, poly amino acid or peptide with the active agentprior to administration.

[0033] The administration mixtures are prepared by mixing an aqueoussolution of the carrier with an aqueous solution of the activeingredient, just prior to administration. Alternatively, the carrier andthe biologically or chemically active ingredient can be admixed duringthe manufacturing process. The solutions may optionally containadditives such as phosphate buffer salts, citric acid, acetic acid,gelatin, and gum acacia.

[0034] Stabilizing additives may be incorporated into the carriersolution. With some drugs, the presence of such additives promotes thestability and dispersibility of the agent in solution.

[0035] The stabilizing additives may be employed at a concentrationranging between about 0.1 and 5% (W/V), preferably about 0.5% (W/V).Suitable, but non-limiting, examples of stabilizing additives includegum acacia, gelatin, methyl cellulose, polyethylene glycol, carboxylicacids and salts thereof, and polylysine. The preferred stabilizingadditives are gum acacia, gelatin and methyl cellulose.

[0036] The amount of active agent is an amount effective to accomplishthe purpose of the particular active agent. The amount in thecomposition typically is a pharmacologically, biologically,therapeutically, or chemically effective amount. However, the amount canbe less than a pharmacologically, biologically, therapeutically, orchemically effective amount when the composition is used in a dosageunit form, such as a capsule, a tablet or a liquid, because the dosageunit form may contain a multiplicity of carrier/biologically orchemically active agent compositions or may contain a dividedpharmacologically, biologically, therapeutically, or chemicallyeffective amount. The total effective amounts can then be administeredin cumulative units containing, in total, pharmacologically,biologically, therapeutically or chemically active amounts ofbiologically or pharmacologically active agent.

[0037] The total amount of active agent, and particularly biologicallyor chemically active agent, to be used can be determined by thoseskilled in the art. However, it has surprisingly been found that withsome biologically or chemically active agents, the use of the presentlydisclosed carriers provides extremely efficient delivery, particularlyin oral, intranasal, sublingual, intraduodenal, or subcutaneous systems.Therefore, lower amounts of biologically or chemically active agent thanthose used in prior dosage unit forms or delivery systems can beadministered to the subject, while still achieving the same blood levelsand therapeutic effects.

[0038] The amount of carrier in the present composition is a deliveryeffective amount and can be determined for any particular carrier orbiologically or chemically active agent by methods known to thoseskilled in the art.

[0039] Dosage unit forms can also include any of excipients; diluents;disintegrants; lubricants; plasticizers; colorants; and dosing vehicles,including, but not limited to water, 1,2-propane diol, ethanol, oliveoil, or any combination thereof.

[0040] Administration of the present compositions or dosage unit formspreferably is oral or by intraduodenal injection.

[0041] The delivery compositions of the present invention may alsoinclude one or more enzyme inhibitors. Such enzyme inhibitors include,but are not limited to, compounds such as actinonin or epiactinonin andderivatives thereof. These compounds have the formulas below:

[0042] Derivatives of these compounds are disclosed in U.S. Pat. No.5,206,384. Actinonin derivatives have the formula:

[0043] wherein R⁵ is sulfoxymethyl or carboxyl or a substituted carboxygroup selected from carboxamide, hydroxyaminocarbonyl and alkoxycarbonylgroups; and R⁶ is hydroxyl, alkoxy, hydroxyamino or sulfoxyamino group.Other enzyme inhibitors include, but are not limited to, aprotinin(Trasylol) and Bowman-Birk inhibitor.

[0044] The compounds and compositions of the subject invention areuseful for administering biologically or chemically active agents to anyanimals such as birds; mammals, such as primates and particularlyhumans; and insects. The system is particularly advantageous fordelivering chemically or biologically or chemically active agents whichwould otherwise be destroyed or rendered less effective by conditionsencountered before the active agent its target zone (i.e. the area inwhich the active agent of the delivery composition are to be released)and within the body of the animal to which they are administered.Particularly, the compounds and compositions of the present inventionare useful in orally administering active agents, especially those whichare not ordinarily orally deliverable.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0045] The following examples illustrate the invention withoutlimitation. All parts are given by weight unless otherwise indicated.

EXAMPLE 1 Carrier Preparation

[0046] General Preparations of Carriers.

[0047] The following procedures were used to prepare the compoundsdescribed herein. Many of the compounds were prepared by reaction of theappropriate amino acid with the appropriate acid chloride. Thepreparation of compound 79 is given as a representative example of thecompounds prepared in this manner.

[0048] Preparation of Compound 79. Method A.

[0049] A 1 L round bottom flask fitted with a magnetic stirrer wascharged with 3-(4-aminophenyl)propionic acid (46.3 g, 0.28 moles, 1.17equiv.) and 2 M aqueous sodium hydroxide (300 mL).2,3-dimethoxybenzoylchloride (48.0 g, 0.24 moles, 1.00 equiv.) was addedportionwise over 1 h to the stirred solution. After the addition, thereaction was stirred for 2.5 h at ambient temperature, and the pH of thesolution was kept at ca 10 by the addition of 10 M sodium hydroxide. Thesolution was then acidified with 1 M hydrochloric acid (3×100 mL), water(100 mL), and air dried. It was redissolved in boiling acetone (ca 500mL), decolorized with activated charcoal (3 g), and filtered. Water (1.5L) was added to the filtrate to induce the formation of a brown oil. Thebrown oil solidified upon stirring at room temperature for 10 min. Thecrude solid was collected by filtration and recrystallized from 70%methanol-water (v/v) to afford compound 79 as a tan solid (39.5) g,50%).

[0050] Compounds 1, 5, 30, 31, 33, 36, 53-66, 68, 69, 71-74, 78, 80-88,95, 97-99, 102, 108-110, 112-115, 119, 121-126, 136, 137, 139, 141, 144,146, 147, 151, 152, 155-158, 160, 161, 163, 165, 166, 170, 172-174, 176,177, 184-186, 188, 189, 191 and 192 were also prepared by this process.

[0051] Preparation of Compound 79. Method B.

[0052] A 2 L three-neck round bottom flask was fitted with a magneticstirrer and two addition funnels under an argon atmosphere. A suspensionof 3-(4-aminophenyl)propionic acid (46.3 g, 0.28 moles, 1.17 equiv.) inethyl acetate (700 mL) was added to the flask. A solution of2,3-dimethoxybenzoylchloride (48.0 g, 0.24 moles, 1.00 equiv.) in ethylacetate (250 mL) was charged to one of the addition funnels and addeddropwise over 1 h. Triethylamine (28.20 g, 0.28 moles, 1.00 equiv.) wassubsequently charged to the second funnel and added dropwise over 15min. The reaction was stirred at ambient temperature for 3 h, and thesolvent was evaporated in vacuo giving a residual brown oil. Water (600mL) was added to the residue followed by sodium hydroxide (2 M, 500 mL),and the mixture was stirred at ambient temperature for 3 hours. Theresultant brown solution was acidified with 2 M hydrochloric acid (ca 1L). After cooling the mixture in an ice bath for 1 h, a yellow solidformed and was collected by filtration. The solid was washed with water(3×1.5 L) and recrystallized from 50% ethanol-water (v/v) to givecompound 79 as a tan solid (59.2 g, 68%).

[0053] Compounds 18, 32, 37, 41, 168, 175, and 183 were also prepared bythis process.

[0054] Preparation of Compound 79. Method C.

[0055] A 2 L round bottom flask equipped with a magnetic stirrer and areflux condenser was charged with a suspension of3-(4-aminophenyl)propionic acid (46.3 g, 0.28 moles, 1.17 equiv.) indichloromethane (560 mL). Chlorotrimethylsilane (62.36 g, 0.57 moles,2.05 equiv.) was added in one portion, and the mixture was heated toreflux for 1 h under argon. The reaction was allowed to cool to roomtemperature and was placed in an ice bath (internal temperature <10°C.). The reflux condenser was replaced with an addition funnelcontaining triethylamine (42.50 g, 0.42 moles, 1.50 equiv.). Thetriethylamine was added dropwise over 15 min, and a yellow solid formedduring the addition. The funnel was replaced by another addition funnelcontaining a solution of 2,3-dimethoxybenzoylchloride (48.0 g, 0.24moles, 1.00 equiv. in dichloromethane (100 mL). The solution was addeddropwise over 30 min. The reaction was stirred in the ice bath foranother 30 min and at ambient temperature for 1 h. The dichloromethanewas evaporated in vacuo to give a brown oil. The brown oil was cooled inan ice bath, and an ice-cold solution of 2 M sodium hydroxide (700 mL)was added. The ice bath was removed, and the reaction was stirred for 2h to afford a clear brown solution. The solution was acidified with 2 Msulfuric acid (400 mL) and stored at ca 5° C. for 1 hour. A yellow solidformed and was collected by filtration. The solid was washed with water(3×100 mL) and recrystallized from 50% ethanol-water (v/v) to affordcompound 79 as tan needles (64.7 g, 82%).

[0056] Compounds 2-4, 6-17, 19-29, 34, 38-40, 42-48, 50-52, 67, 70,75-77, 89-94, 96, 100, 101, 107, 111, 116-118, 127-132, 134, 135, 193,142, 143, 148, 149, 159, 162, 164, 169, 178-182, 187, and 190 were alsoprepared by this process.

[0057] Preparation of Compound 35.

[0058] A solution of O-acetylsalicyloyl chloride (24.68 g, 124 mmol, 1equiv) in tetrahydrofuran (300 mL) was cooled in an ice bath.Triethylamine (25 g, 249 mmol, 2 equiv) was added dropwise via anadditional funnel. The methyl 9-aminononanoate hydrochloride wasdissolved in DMF (190 mL, slightly warm to dissolve), charged to anaddition funnel and added dropwise to the above mixture. The reactionwas stirred in the ice-bath for 20 min and at room temperature for 2 h.Evaporation of the THF under reduced pressure gave a pink DMF solution.The pink solution was cooled in an ice-bath, and 2 M aqueous sodiumhydroxide (300 mL) was added. After being stirred at room temperaturefor 12 h, the mixture was acidified with 2 M hydrochloric acid (500 mL).The solution was cooled in an ice-bath, and a solid formed. The solidwas collected by filtration and was recrystallized from 50%ethanol/water to give compound 35 (32 g, 87%) as an off-white solid.

[0059] Preparation of Compound 49.

[0060] 1-(2-hydroxyphenyl)-3-(4-methyl benzoate)-1,3-propane dione (3.00g, 0.0101 mil.) is placed in a 100 ml round bottomed flask fitted withargon purge, magnetic stir bar and cold water condenser. Glacial aceticacid (20 mls) and concentrated sulfuric acid (5 mls) were added, andheating of the reaction mixture was initiated. The reaction mixture wasallowed to heat at reflux for 6 h before heating was discontinued. Thereaction mixture was allowed to come to room temperature, and then waspoured into 100 mls of ice/water. This was stirred for approximately ½ hbefore the mixture was filtered, and a brown solid was isolated. Thebrown solid was recrystallized twice from acetic acid, yielding compound49 as a tan solid (1.44 g, 53.8%).

[0061] Preparation of Compound 167.

[0062] 2-coumaranone (4.21 g, 0.0314 mol) was dissolved, with stirring,in acetonitrile (75 mls) in a 250 ml round bottomed flask fitted with amagnetic stir bar, argon purge and cold water condenser. Triethylamine(3.18 g, 0.0314 mol) and 8-aminocaprylic acid (5.00 g, 0.0314 mol) wereadded, and a tan slurry was formed. Heating was started, and thereaction mixture was allowed to reflux overnight. After heatingovernight, thin layer chromatography of the reaction mixture (50% ethylacetate/50% hexane) indicated that the reaction had gone to completion.Heating was stopped, the reaction mixture was allowed to cool to roomtemperature, and was concentrated in vacuo. The resulting residue wastaken up in methylene chloride, and was washed with two, 100 ml portionsof 1N hydrochloric acid solution. The methylene chloride layer was driedwith sodium sulfate and was concentrated in vacuo. The resulting tansolid was allowed to dry in vacuo overnight, yielding compound 167 as atan solid (8.35 g, 70.4%).

[0063] Preparation of Compound 171.

[0064] 1,4-benzodioxan-2-one (3.93 g, 0.0262 mol) was dissolved, withstirring, in acetonitrile (70 mls) in a 250 ml round bottomed flaskfitted with a magnetic stir bar, argon purge and cold water condenser.Triethylamine (2.64 g, 0.0262 mol) and 8-aminocaprylic acid (500 g,0.0262 mol) were added and a tan slurry was formed. Heating was started,and the reaction mixture was allowed to reflux for approximately 3hours. At this time, thin layer chromatography of the reaction mixture(50% ethyl acetate /50% hexane) indicated that the reaction had gone tocompletion. Heating was discontinued, and the reaction mixture wasallowed to cool to room temperature and was concentrated in vacuo. Theresulting residue was taken up in methylene chloride and was washed witha 100 ml portion of 1 N hydrochloric acid solution. At this time, a tansolid was noted to precipitate, and it was isolated by filtration. Thistan solid was washed further with an additional 100 ml portion of 1 Nhydrochloric acid solution, and then with 100 ml of water. The resultingtan solid was allowed to dry in vacuo overnight yielding Compound 171 asa tan solid (7.73 g, 95.6%).

[0065] Preparation of Compound 120.

[0066] A solution of 3.00 g (18.3 mmol) of 2-nitrophenylisocyanate and 5mL of tetrahydrofuran was dropwise over 10 min to an ice bath-cooledsolution of 2.08 g (13.1 mmol) of 8-aminocaprylic acid, 1.40 mL of 10 NNaOH and 40 mL of water. The reaction mixture was stirred an additional30 min, warmed to 25° C. and treated with 3% HCl solution until the pHwas 5. The yellow precipitate was filtered off and rinsed with 100 ml ofwater. The yellow solid was recrystallized in 2-propanol and water togive 3.7 g of compound 120 as pale yellow crystals.

[0067] Compounds 104-106 were also prepared by this procedure.

[0068] Preparation of Compound 133.

[0069] A suspension of 2.40 g (16.3 mmol) and 2.80 g (15.6 mmol) of4-(4aminophenyl)butyric acid in 20 mL of propylene glycol, 2.40 mL (1.74g, 17.3 mmol) of triethylamine and 10 mg (0.08 mmol) ofdimethylaminopyridine was heated to 140° C. The mixture became a clearsolution after 5 min at 140° C. After stirring for 330 min, the reactionmixture was cooled to 25° C. and diluted with 20 mL of water. The solidphthalimide which had formed was filtered off. The filtrate wasacidified with 3% HCl solution. The resulting solid was filtered off andwas recrystallized from 2-propanol and water to give 0.62 g of compound133 as a tan solid.

[0070] Preparation of Compound 138.

[0071] A solution of 1.73 g (12.9 mmol) of phthalic dialdehyde, 2.04 g8-aminocaprylic acid and 20 mL of acetic acid was heated to reflux for10 min. The reaction mixture was cooled to 40° C., diluted with waterand extracted with CH₂Cl₂ (2×20 mL). The organic phase was washed withwater and brine, dried over Na₂SO₄ and evaporated. The residue wasdissolved in ether and extracted with 2N NaOH. The layers wereseparated. The aqueous layer was made acidic with 3% HCl and extractedwith CH₂Cl₂. The organic phase was dried over Na₂SO₄ and evaporated. Theyellow residue was crystallized from acetonitrile and water to give 1.25g of compound 138 as a yellow solid.

[0072] Preparation of Compound 140.

[0073] A mixture of 1.40 g (9.48 mmol) of phthalic anhydride and 1.51 g(9.48 mmol) of 8-aminocaprylic acid was heated to 150° C. for 5 min.Upon cooling, 2.61 g of solid compound 140 was received.

[0074] Compound 150 was also prepared by this procedure.

[0075] Preparation of Compound 145.

[0076] A suspension of 2.11 g (10.1 mmol) ethyl carbamoylanthranilicacid and 5 mL of CH₂Cl₂ was treated with 2.20 mL of oxalyl chloride.After stirring for 1 h the volatiles were stripped off. At that sametime, a suspension of 1.60 g (10.1 mmol) of 8-aminocaprylic acid and 15mL of CH₂Cl₂ was treated with 2.60 mL (2.23 g, 20.5 mmol) of TMSCI. Thismixture was heated to reflux for 90 min, cooled in an ice bath andtreated with 4.30 mL (3.12 g, 30.9 mmol) of triethylamine. Five minlater, a slurry of the residue from the oxalyl chloride reaction in 20mL of CH₂Cl₂ was added. The reaction mixture was warmed to 25° C. andstirred overnight. Upon acidification of the mixture with 3% HCl, awhite solid formed. The solid was filtered off and recrystallized fromEtOH and water to give 1.88 g of compound 145.

[0077] Compound 153 was also prepared by this procedure.

[0078] Preparation of Compound 154.

[0079] A suspension of 4.02 g(25.6 mmol) oftrans-4-aminomethylcyclohexane-carboxylic acid, 4.18 g (25.6 mmol) ofisatoic anhydride, 20 mL of CH₂Cl₂, 20 mL of dioxane, and 4 mL of waterwas heated to reflux for 12 h. The solution was cooled to 25° C. andextracted with ether (4×20 mL). The organic layer was dried over Na₂SO₄and concentrated. The resulting solid was recrystallized from EtOH andwater to give 4.95 g of compound 154.

[0080] Compound 103 is available from Aldrich Chemical Company, Inc.,Milwaukee, Wis.

EXAMPLE 2 Parathyroid Hormone Dosing Solutions

[0081] Intracolonic (“IC”) dosing compositions containing 100 mg/kg ofcarrier and 25 μg/kg of parathyroid hormone in 25% aqueous propyleneglycol or oral gavage “PO”) dosing solution containing 400 mg/kg ofcarrier and 100 μg/kg of parathyroid hormone in water, were preparedwith carriers 9, 33, 35, 77, 79, 109, 110, 123, 136, 141, and 169. Thedosing solutions are designated P-carrier number-DS.

COMPARATIVE EXAMPLE 2A Parathyroid Hormone Dosing Solutions

[0082] An intracolonic dosing composition containing 100 mg/kg of acarrier having the formula

[0083] and 25 ug/kg of parathyroid hormone in 25% aqueous propyleneglycol was prepared. The dosing solution is identified as P-9A-DS.

EXAMPLES 3 In vivo Parathyroid Hormone Delivery

[0084] Male Sprague-Dawley rats weighing between 200-250 g were fastedfor 24 hours and were administered ketamine (44 mg/kg) andchlorpromazine (1.5 mg/kg) 15 minutes prior to dosing. The rats wereadministered one of dosing solutions P-9-DS, P-33-DS, P-35-DS, P-77-DS,P-79-DS, and P-141-DS by oral gavage (“PO”) or intra-colonicinstillation (“IC”). Blood samples were collected serially from the tailartery for serum determination of parathyroid hormone concentration.Serum parathyroid hormone concentrations were quantified by aparathyroid hormone immunoaccuracy test host.

[0085] Results are illustrated in Table 2, below.

COMPARATIVE EXAMPLE 3A In vivo Parathyroid Hormone Delivery

[0086] The procedure of Example 3 was followed substituting dosingsolution P-9A-DS for dosing solution P-9-DS. Results are illustrated inTable 2, below.

COMPARATIVE EXAMPLE 3B In vivo Parathyroid Hormone Delivery

[0087] The procedure of Example 3 was followed with a dosing solution(at a dose of 25 μg/kg of parathyroid hormone (intra-colonic) or 100μg/kg of parathyroid hormone (oral)), P-ØA-DS, that omitted the carrier.

[0088] Results are illustrated in Table 2, below. TABLE 2 In vivaParathyroid Hormone Delivery Mean Peak Serum [PTH] ± Dosing SolutionStandard Deviation (pg/ml) P-9-DS 155 ± 105 (IC) P-33-DS 58 ± 18 (IC)P-35-DS 50 ± 27 (IC) P-77-DS 358 ± 274 (PO) P-79-DS 521 ± 128 (PO)P-109-DS 128 ± 25 (IC) P-110-DS 35 ± 11 (IC) P-123-DS 49 ± 22 (IC)P-136-DS 106 ± 72 (IC) P-141-DS 120 ± 120 (PO) P-169-DS 19 ± 33 (IC)P-9A-DS 116 ± 48 (IC) P-0A-DS 11 ± 2 (PO), 27 ± 27 (IC)

EXAMPLES 4 Recombinant Human Growth Hormone Dosing Solutions

[0089] Intracolonic dosing compositions containing 25 mg/kg of carrierand 1 mg/kg of rHGH in phosphate buffer or oral gavage dosing solutionscontaining 600 mg/kg of carrier and 3 mg/kg of rHGH in phosphate bufferwere prepared with carriers 9, 35, 36, 47, 62, 64, 67, 77, 79, 90, 94,107, 109, 136, and 141.

[0090] The dosing solutions are designated R-carrier number-DS.

COMPARATIVE EXAMPLE 4A Recombinant Human Growth Hormone Dosing Solutions

[0091] An intracolonic dosing solution was prepared according to theprocedure of Example 4, substituting a carrier having the formula

[0092] for the carrier. This dosing solution is designated as R-35A-DS.

COMPARATIVE EXAMPLE 4B Recombinant Human Growth Hormone Dosing Solutions

[0093] An intracolonic dosing solution was prepared according to theprocedure of Example 4, substituting a carrier having the formula

[0094] for the carrier. This dosing solution is designated as R-35B-DS.

COMPARATIVE EXAMPLE 4C Recombinant Human Growth Hormone Dosing Solutions

[0095] An intracolonic dosing solution was prepared according to theprocedure of Example 4, substituting a carrier having the formula

[0096] for the carrier. This dosing solution is designated as R-9A-DS.

EXAMPLE 5 In vivo Recombinant Human Growth Hormone Delivery

[0097] Male Sprague-Dawley rats weighing 200-250 g were fasted for 24hours and administered ketamine (44 mg/kg) and chlorpromazine (1.5mg/kg) 15 minutes prior to dosing. The rats were administered one of thedosing solutions of Example 3 by either oral gavage or intracolonicinstillation. Blood samples were collected serially from the tail arteryfor determination of serum rHGH concentrations. Serum rHGHconcentrations were quantified by an rHGH immunoassay test kit.

[0098] Results are illustrated in Table 3, below.

COMPARATIVE EXAMPLE 5A In vivo Recombinant Human Growth Hormone Delivery

[0099] The procedure of Example 5 was followed, substituting the dosingsolutions of Comparative Examples 3A-3C for the dosing solutions.Results are illustrated in Table 3, below.

COMPARATIVE EXAMPLE 5B In vivo Recombinant Human Growth Hormone Delivery

[0100] The procedure of Example 5 was followed, with dosing solutions ofactive agent (at a dose of 1 mg of rHGH/kg (intracolonic) or 3 mg ofrHGH/kg (oral) and no carrier. These dosing solutions are designatedR-ØD-DS and R-ØE-DS, respectively. Results are illustrated in Table 3,below. TABLE 3 In Vivo Recombinant Human Growth Hormone Delivery MeanPeak Serum [rHGH] ± Dosing Solution Standard Deviation (ng/ml) R-9-DS125 ± 34 (IC) R-35-DS 41 ± 46 (PO) 108 ± 56 (IC) R-36-DS 28 ± 11 (IC)R-47-DS 0 (IC) R-62-DS 11 ± 12 (IC) R-64-DS 72 ± 22 (PO) R-67-DS 19 ± 22(PO) 88 ± 24 (IC) R-77-DS 34 ± 10 (PO) R-79-DS 62 ± 51 (PO) R-90-DS 9 ±13 (PO) R-94-DS 39 ± 35 (PO) R-107-DS 0 ± 0 (PO) R-109-DS 128 ± 25 (IC)R-136-DS 106 ± 72 (IC) R-141-DS 95 ± 14 (IC) R-35A-DS 17 ± 3 (IC)R-35B-DS 42 ± 28 (IC) R-9A-DS 55 ± 17 (IC) R-0D-DS 0 ± 0 (IC) R-0E-DS 0± 0 (IC)

EXAMPLE 6 In vivo Interferon Delivery

[0101] An intracolonic dosing composition containing 50 mg/kg of carrier9 and 250 μg/kg of interferon in 50% propylene glycol was prepared. Ratswere administered the dosing composition by intracolonic instillation.Delivery was evaluated by use of an ELISA assay for human interferon αfrom Biosource, Inc. Mean peak serum interferon concentration was2611±695.

COMPARATIVE EXAMPLE 6A In vivo Interferon Delivery

[0102] Rats were administered, orally and by intracolonic instillation,dosing solutions of 1 mg/kg of interferon and no carrier. Delivery wasevaluated according to the procedure of Example 6. Mean peak seruminterferon concentration was 1951±1857 (PO) and 79±100 (IC).

EXAMPLE 7 Heparin Dosing Solutions

[0103] Intracolonic dosing compositions containing 50 mg/kg of carrierand 25 mg/kg of heparin in 25% aqueous propylene glycol or oral gavagedosing solutions containing 300 mg/kg of carrier and 100 mg/kg ofheparin in 25% aqueous propylene glycol were prepared with carriers 9,35, 47, 50, 58, 62, 64, 67, 76, 96, 102, 109, 110, 111, 117, 122, 123,139, 141, 144, and 169. The dosing solutions are designated H-carriernumber-DS.

COMPARATIVE EXAMPLE 7A Heparin Dosing Solutions

[0104] Comparative intracolonic dosing compositions were preparedaccording to the procedure of Example 7, substituting the followingcarriers for the carrier.

[0105] These dosing solutions are designated H-35A-DS, H-35B-DS, andH-109A-DS, respectively.

EXAMPLES 8 In vivo Evaluation of Heparin in Rats

[0106] The dosing solutions of Example 7 were administered to fastedrats either by oral gavage or intracolonic instillation.

[0107] Blood samples were collected by cardiac puncture following theadministration of ketamine (44 mg/kg). Heparin activity was determinedby utilizing the activated partial thromboplastin time (APTT) accordingto the method of Henry, J. B., Clinical Diagnosis and Management byLaboratory Methods; Philadelphia, Pa.; W. B. Saunders (1979).

[0108] Results are in illustrated in Table 4, below.

COMPARATIVE EXAMPLES 8A In vivo Evaluation of Heparin in Rats

[0109] The dosing solutions of Comparative Example 7A were administeredto fasted rats by intracolonic instillation. Blood samples werecollected and heparin activity was determined by the method of Example8.

[0110] Results are illustrated in Table 4, below.

COMPARATIVE EXAMPLE 8B In vivo Evaluation of Heparin in Rats

[0111] An intracolonic dosing solution of 25 mg/kg of heparin and anoral gavage dosing solution of 100 mg/kg of heparin were administered tofasted rats. These dosage solutions were designated H-ØA-DS and H-ØB-DS,respectively.

[0112] Blood samples were collected, and heparin activity was determinedby the methods of Example 8.

[0113] Results are illustrated in Table 4, below. TABLE 4 In VivoEvaluation of Heparin in Rats Dosing Solution Heparin APTT (sec) H-9-DS48 ± 18 (IC) H-35-DS 54 ± 27 (PO), 177 ± 85 (IC) H-47-DS 30 ± 14 (IC)H-50-DS 40 ± 22 (IC) H-58-DS 24 ± 4 (IC) H-62-DS 37 ± 13 (IC) H-64-DS 59± 28 (PO), 168 ± 75 (IC) H-67-DS 76 ± 36 (IC) H-76-DS 63 ± 27 (PO)H-96-DS 36 ± 8 (IC) H-102-DS 111 ± 108 (IC) H-109-DS 56 ± 28 (IC)H-110-DS 37 ± 9 (IC) H-111-DS 71 ± 39 (IC) H-117-DS 140 ± 128 (IC)H-122-DS 49 ± 21 (IC), 207 ± 7 (PO) H-123-DS 42 ± 14 (PO) H-139-DS 31 ±11 (IC) H-141-DS 59 ± 26 (IC) H-144-DS 26 ± 3 (IC) H-35A-DS 61 ± 29 (IC)H-35B-DS 51 ± 30 (IC) H-169-DS 23 ± 2 (IC) H-0A-DS 23 ± 2 (PO) H-0B-DS33 ± 6 (IC)

[0114] The above mentioned patents, applications, test methods, andpublications are hereby incorporated by reference in their entirety.

[0115] Many variations of the present invention will suggest themselvesto those skilled in the art in light of the above detailed description.All such obvious variations are within the full intended scope of theappended claims.

What is claimed is:
 1. A composition comprising: (A) at least one activeagent; and (B) at least one carrier selected from the group consistingof

1 6-N-(3,5-dichloro-2-hydroxybenzoyl)aminocaproic acid

2 8(2-aminobenzoylamino)caprylic acid

3 8(2-trifluoromethoxy)benzoylamino caprylic acid

4 N-(2-hydroxybenzoyl)isonipecotic acid

5 4-[4-(2-aminobenzoylamino)phenyl]butyrylhydroxamic acid

6 4-(4-(pentafluorobenzoyl)aminophenyl)butyric acid

7 4-(4-(3-anisoyl)aminophenyl)butyric acid

8 8-(3-anisoyl)aminocaprylic acid

10 4-(4-(2-nitrobenzenesulfonyl)aminophenyl)butyric acid

11 8-(2-nitrobenzenesulfonyl)aminocaprylic acid

12 6-(4-salicyloyl)aminophenyl)hexanoic acid

13 8-(2-methoxybenzoyl)amino caprylic acid

14 2-[4-Salicyloylamino)phenyl]ethyl methyl sulfone

15 1-Salicyloyl-2-succinyl hydrazide

16 3-(4-(2,5-dimethoxycinnamoyl)aminophenyl)propionic acid

17 4-(4-(2,5-dimethoxycinnamoyl)aminophenyl)butyric acid

18 1-salicyloyl-2-glutaryl hydrazide

19 Succinyl-4-aminosalicylic acid

20 8-(Phenoxyacetylamino)caprylic acid

21 8-(2-pyrazinecarbonyl)aminocaprylic acid

22 4-(4-(2-pyrazinecarbonyl)aminophenyl)butyric acid

23 6-(4-(N-2-Nitrobenzoyl)aminophenyl)hexanoic acid

24 6-(4-(N-2-aminobenzoyl)aminophenyl)hexanoic acid

25 4-(4-(2-(3-carboxyl)pyrazinecarboxyl)aminophenyl)butyric acid

26 4(2-Nitrobenzoyl)aminophenylsuccinic acid

27 8-(2-(trifluoromethoxy)benzoyl)aminocaprylic acid

28

29 8-(Benzylcarbonylamino)caprylic acid

30 8-(phenylcarbonylamino)caprylic acid

31 2-[4-(2-Methoxybenzoylamino)phenyl]ethyl H₂PO₄

32 1-salicyloyl-2-suberyl hydrazide

33 4-(4-benzyloxycarbonylaminophenyl)butyric acid

34 4-(4-(2-hydroxynicotinoyl)aminophenyl)butyric acid

36 4-(4-phenyloxycarbonylaminophenyl)butyric acid

37 3-(2-methoxybenzoylamino)-1-propanol

38 8-(2-Hydroxynicotinoyl)aminocaprylic acid

39 6-(2-methoxybenzoyl)amino nicotinic acid

40 salicyloylglycine

41 4-(1-(2-pyrimidyl)piperazinoyl)butyric acid

42 8-(chromone-3-carbonyl)aminocaprylic acid

43 8-(vinylbenzoyl)aminocaprylic acid

44 4-(4-(chromone-3-carbonyl)aminophenyl)butyric acid

45 8-cinnamoylaminocaprylic acid

46 5-(N-salicyloylamino)valeric acid

47 9-(2-hydroxybenzamido)nonanic acid

48 N-(4-salicyloylamino)-6-caproic acid

49 4′-flavonic acid

50 11-cinnamoylaminoundecanoic acid

51 4-octanoylamino-3-hydroxybanzoic acid

52 (3Phenyl2,3-dihydroxypropanoyl)8aminocaprylic acid

53 8-[N-(3-coumarincarbonyl)]aminocaprylic acid

54 8-[N-(4-chlorobenzoyl)]aminocaprylic acid

55 8-[N-3-fluorobenzoyl)]aminocaprylic acid

56 8-(N-2,5-Dihydroxybenzoyl)aminocaprylic acid

57 8-(N-2,3-Dimethoxybenzopyl)aminocaprylic acid

58 8-(N-2,4-Dihydroxybenzoyl)aminocaprylic acid

59 8-(N-2,5-Dimethoxybenzoyl)aminocaprylic acid

60 8-(N-3,5-Diacetyloxybenzoyl)aminocaprylic acid

61 8-(N-4-Hydroxybenzoyl)aminocaprylic acid (dimer)

62 8-(N-2,4-Dihydroxybenzoyl)aminocaprylic acid

63 10-(N-2-Methoxyanilino)sebalic acid

65 2-Methoxybenzeneaminodecanoic acid

66 8-(N-benzoyl)aminocaprylic acid

68 8-[N-(4-fluorobenzoyl)]aminocaprylic acid

69 8-[N-(2-bromobenzoyl)]aminocaprylic acid

70 8-(4-(1,2-dihydroxyethyl)benzoyl)aminocaprylic acid

71 8-[N-(4-bromobenzoyl)]aminocaprylic acid

72 8-[N-(4-iodobenzoyl)]aminocaprylic acid

73 4-{4-[N-(2-iodobenzoyl)aminophenyl]}butyric acid

74 4-{4-[N-(1-hydroxy-2-naphthoyl)aminophenyl]}butyric acid

75 4-(4-(2,4-dimethoxybenzoyl)aminophenyl)butyric acid

76 4-(o-anisoyl)aminophenylacetic acid

77 3-[4-(2,4-dimethoxybenzoyl) aminophenyl] propionic acid

78 4-{4-[N-(4-iodobenzoyl)] aminophenyl} butyric acid

80 4{4-[N-2-bromobenzoyl)] aminophenyl} butyric acid

81 4{4-[N-3-bromobenzoyl) aminophenyl]} butyric acid

82 8-(N-3,5-Dihydroxybenzoyl)aminocaprylic acid

83 8-(N-3,5-Dimethoxy 4-hydroxybenzoyl)aminocaprylic acid

84 8-(N-2-6-Dimethoxybenzoyl)aminocaprylic acid

85 4-{4-[N-(4-bromobenzoyl)aminophenyl]}butyric acid

86 8-(2-hydroxy-4-chlorobenzoyl)aminocaprylic acid

87 8-(N-2,6-Dihydroxybenzoyl)aminocaprylic acid

88 8-(N-Hydroxy6-methoxybenzoyl)aminocaprylic acid

89 8-(5-chloro-o-anisoyl)aminocaprylic acid

90 4-(4-(2,3-dimethoxybenzoyl)aminophenyl)butyric acid

91 4-(4-(5-chloro-o-anisoyl)aminophenyl)butyric acid

92 4-(4-(4-chloro-o-anisoyl)aminophenyl)butyric acid

93 8-(4-chloro-o-anisoyl)aminocaprylic acid

94 3-(4-(2,5-dimethoxybenzoyl)aminophenyl)propionic acid

95 4-{N-[4-(3-iodobenzoyl)aminophenyl]}butyric acid

96 7-cinnamoylaminoheptanoic acid

97 8-N-(3-iodobenzoyl)aminocaprylic acid

98 8-N-(4-methoxy-3-nitrobenzoyl)aminocaprylic acid

99 8-N-(2-methoxy-4-nitrobenzoyl)aminocaprylic acid

100 4-{N-[4-(2-methoxy-4-nitrobenzoyl)aminophenyl]}butyric acid

101 4-(4-(2,5-dimethoxybenzoyl)aminophenyl)butyric acid

103 3-Indolebutyric acid

104

105

106

108 4-[4-N-(4-methoxy-3-nitrobenzoyl)aminophenyl]butyric acid

110 8-(N-2-hydroxy-5-iodobenzoyl)aminocaprylic acid

112 8-(N-2-hydroxy-4-nitrobenzoyl)aminocaprylic acid

113 4-[-N-(2-hydroxy-4-bromobenzoyl)aminophenyl]butyric acid

114 8-(N-2,3-Dihydroxybenzoyl)aminocaprylic acid

115 8-(N-3-methylsalicyloyl)aminocaprylic acid

116 8-(N-5-methylsalicyloyl)aminocaprylic acid

118 4-(4-(2-chloro-5-nitrobenzoyl)aminophenyl)butyric acid

119 4-{-[N-(2hydroxy-5-iodobenzoyl)]aminopheny;}butyric acid

120 N-2-nitrophenyl-N′-(8-octanoic acid) urea

121 N-(2-methoxy-5-nitrophenyl) sebecoyl amide acid

123 8-[N-(2-acetoxy-3,5-dibromobenzoyl)]aminocaprylic acid

124 8-N-(2-chloro-6-fluorobenzoyl)aminocaprylic acid

125

126 8-N-(4-hydroxy-3-nitrobenzoyl)caprylic acid

127 4-(4-Salicyloylaminophenyl)-4-oxobutyric acid

128 12-cinnamoyldodecanoic acid

129 4-{4-[N-(3-hydroxy-2-naphthoyl)aminophenyl]}butyric acid

130 8-(4-chloro-3-nitrobenzoyl)aminocaprylic acid

131 8-(2-chloronicotinoyl)aminocaprylic acid

132 8-(2-chloro-5-nitrobenzoyl)aminocaprylic acid

133 4-(4-phthalimidophenyl)butyric acid

134 4-{4-[N-(3-hydroxy-2-naphthoyl)aminophenyl]}propanoic acid

135 3-(4-(2,6-dimethoxybenzoyl)aminophenyl)propionic acid

137 8-(N-2-chloro-4-fluorobenzoyl)aminocaprylic acid

138 8-(2-(1,2-dihydroisoindole-1-one))octanoic acid

139 8-(N-1-hydroxy-2-naphthoyl)aminocaprylic acid

140 8-(phthalimido)caprylic acid

142 6-(anisoyl)aminocaproic acid

143 4-(4-(4-chloro-3-ribobenzoyl)aminophenyl)butyric acid

144 11-N-(1-hydroxy-2-naphthoyl)aminoundecanoic acid

145 Bis(N-2carboxylphenyl-N-(N′-8-octanoic acid)ureal)oxalyl diamide

146 2-[2-N-(2-chlorobenzoyl)aminoethoxy]ethanol

147 2-[2-(4-chlorobenzoyl)aminoethoxy]ethanol

148 4-(2-methoxybenzoyl)amino 3-carboxysulfoxide

149 4-(2-methoxybenzoyl)amino 3-carboxypropylsulfone

150 4-(4-(3-hydroxyphthalimido)phenyl)butyric acid

151 2-[2-N-(2-methoxybenzoyl)aminoethoxy)]ethanol

152 2-[2-N-(3-chlorobenzoyl)aminoethoxy)]ethanol

153 Bis(M-2-carboxyphenyl-N-(N′-3(4-aminophenyl)propionicacid)ureal)oxalyl diamide

154 trans-4-(2-aminobenzamidomethyl)cyclohexamecarboxylic acid

155 11-N-(3,5-dichloro-2-hydroxybenzoyl)aminoundecanoic acid

156 2-[N-(2-bromobenzoyl)aminoethoxy]ethanol

157 7-N-(3,5-dichloro-2-hydroxybenzoyl)aminoheptanoic acid

158 N-[3,5-dichloro-2-hydroxybenzoyl-4(4-aminophenyl)]butyric acid

159 trans-4-(N-salicyloylaminomethyl)cyclohexane carboxylic acid

160 N-[3,5-dichloro-2-hydroxybenzoyl-3-(4-aminophenyl)]propionic acid

161 12-N-(3,5-dichloro-2-hydroxybenzoyl)aminododecanoic acid

162 N-(2-hydroxy-4-carboxy)-6-heptenamide

163 N-(2-bromobenzoyl)morpholine

164 8-N-cyclohexanoylaminocaprylic acid

165 2-[N-(2-iodobenzoyl)aminoethoxy]ethanol

166 5-(4-chloro-2-hydroxyanilinocarbonyl)valeric acid

167 8-(2-hydroxyphenoxyl)-aminocaprylic acid

168 N-Salicyloyl-5-(3-aminophenyl)valeric acid

169 4-(4-(2-ethoxylbenzoyl)aminophenyl)butyric acid

170 9-[2-(3-hydroxy)pyridylaminocarbonyl] nananic acid

171 7-(2-hydroxyphenoxyacetyl)aminocaprylic acid

172 2-[N-(2-hydroxybenzoylamino)ethoxy]ethanol

173 4-[N-(3,5-dichloro-2-hydroxybenzoyl)]aminophenylacetic acid

174 8-(2-hydroxy-5-chloroanilinocarbonyl)octanoic acid

175 N-salicyloyl-5-(4-aminophenyl)valeric acid

176 9-(2-hydroxy-5-methylanilinocarbonyl)nonanionic acid

177 5-(2-hydroxy-5-methylanilinocarbonyl)valeric acid

178 8-(pentafluorobenzoyl)aminocaprylic acid

179 3-(3-(salicyloyl)aminophenyl)propionic acid

180 8-(2-ethoxybenzoyl)aminocaprylic acid

181 4-(4-(2-Dimethylamino benzoic)aminophenyl)butyric acid

182 8-(3-Phenoxypropionylamino)caprylic acid

183 4-(Salicyloyl)aminophenylethyltetrazole

184 8(-(4(N-salicyloyl-4aminophenyl)butyric)aminocaprylic acid [sic]

185 4-(4-(N-(2-Fluorocinnamoyl)aminophenyl) butyric

186 4-(4-(N-8(N-Salicyloyl)aminocaprylic)aminophenyl)butyric acid

187 8-(p-anisoyl)aminocaprylic acid

188 8-(4-Hydroxybenzoyl)aminocaprylic acid

189 8-(3-Hydroxybenzoyl)aminocaprylic acid

190 8-(3,4,5-Trimethoxybenzoyl)aminocaprylic acid

191 8-(N-4-Methylsalicyloyl)aminocaprillic acid [sic]

192 N-10-(2-hydroxy-5-nitroanilino)decanoic acid

193 4-(4-(2-chloronicotinoyl)aminophenyl)butyric acid

and a salt of any of the foregoing.
 2. A composition as defined in claim1, wherein said active agent is selected from the group consisting of abiologically active agent, a chemically active agent, or a combinationthereof.
 3. A composition as defined in claim 2, wherein saidbiologically active agent comprises at least one peptide,mucopolysaccharide, carbohydrate, or lipid.
 4. A composition as definedin claim 2, wherein said biologically active agent is selected from thegroup consisting of human growth hormone, bovine growth hormone, growthhormone-releasing hormone, an interferon, interleukin-II, insulin,heparin, low molecular weight heparin, calcitonin, erythropoietin,atrial naturetic factor, an antigen, a monoclonal antibody,samatostatin, adrenocorticotropin, gonadotropin releasing hormone,oxytocin, vasopressin, cromolyn sodium, vancomycin, parathyroid hormone,desferrioxamine (DFO), or any combination thereof.
 5. A composition asdefined in claim 4, wherein said biologically active agent comprises aninterferon, interleukin-II, insulin, heparin, low molecular weightheparin, calcitonin, oxytosin, vasopressin, vancomycin, DFO, parathyroidhormone, and combinations thereof.
 6. A composition as defined in claim1, wherein said carrier comprises a poly(amino acid).
 7. A compositionas defined in claim 1, wherein said carrier comprises a polypeptide. 8.A dosage unit form comprising (A) a composition as defined in claim 1;and (B) (a) an excipient (b) a diluent, (c) a disintegrant, (d) alubricant, (e) a plasticizer, (f) a colorant, (g) a dosing vehicle, or(h) any combination thereof.
 9. A composition as defined in claim 8,wherein said active agent is selected from the group consisting of abiologically active agent, a chemically active agent, or a combinationthereof.
 10. A composition as defined in claim 9, wherein saidbiologically active agent comprises at least one peptide,mucopolysaccharide, carbohydrate, or lipid.
 11. A composition as definedin claim 9, wherein said biologically active agent is selected from thegroup consisting of human growth hormone, bovine growth hormone, growthhormone-releasing hormone, an interferon, interleukin-II, insulin,heparin, low molecular weight heparin, calcitonin, erythropoietin,atrial naturetic factor, an antigen, a monoclonal antibody,samatostatin, adrenocorticotropin, gonadotropin releasing hormone,oxytocin, vasopressin, cromolyn sodium, vancomycin, parathyroid hormone,desferrioxamine (DFO), or any combination thereof.
 12. A composition asdefined in claim 11, wherein said biologically active agent comprises aninterferon, interleukin-II, insulin, heparin, low molecular weightheparin, calcitonin, oxytosin, vasopressin, vancomycin, DFO, parathyroidhormone, and combinations thereof.
 13. A dosage unit form comprising (A)a composition as defined in claim 6; and (B) (a) an excipient (b) adiluent, (c) a disintegrant, (d) a lubricant, (e) a plasticizer, (f) acolorant, (g) a dosing vehicle, or (h) any combination thereof.
 14. Acomposition as defined in claim 13, wherein said active agent isselected from the group consisting of a biologically active agent, achemically active agent, or a combination thereof.
 15. A composition asdefined in claim 14, wherein said biologically active agent comprises atleast one peptide, mucopolysaccharide, carbohydrate, or lipid.
 16. Acomposition as defined in claim 14, wherein said biologically activeagent is selected from the group consisting of human growth hormone,bovine growth hormone, growth hormone-releasing hormone, an interferon,interleukin-II, insulin, heparin, low molecular weight heparin,calcitonin, erythropoietin, atrial naturetic factor, an antigen, amonoclonal antibody, samatostatin, adrenocorticotropin, gonadotropinreleasing hormone, oxytocin, vasopressin, cromolyn sodium, vancomycin,parathyroid hormone, desferrioxamine (DFO), or any combination thereof.17. A composition as defined in claim 16, wherein said biologicallyactive agent comprises an interferon, interleukin-II, insulin, heparin,low molecular weight heparin, calcitonin, oxytosin, vasopressin,vancomycin, DFO, parathyroid hormone, and combinations thereof.
 18. Adosage unit form comprising (A) a composition as defined in claim 7; and(B) (a) an excipient (b) a diluent, (c) a disintegrant, (d) a lubricant,(e) a plasticizer, (f) a colorant, (g) a dosing vehicle, or (h) anycombination thereof.
 19. A composition as defined in claim 18, whereinsaid active agent is selected from the group consisting of abiologically active agent, a chemically active agent, or a combinationthereof.
 20. A composition as defined in claim 19, wherein saidbiologically active agent comprises at least one peptide,mucopolysaccharide, carbohydrate, or lipid.
 21. A composition as definedin claim 19, wherein said biologically active agent is selected from thegroup consisting of human growth hormone, bovine growth hormone, growthhormone-releasing hormone, an interferon, interleukin-II, insulin,heparin, low molecular weight heparin, calcitonin, erythropoietin,atrial naturetic factor, an antigen, a monoclonal antibody,samatostatin, adrenocorticotropin, gonadotropin releasing hormone,oxytocin, vasopressin, cromolyn sodium, vancomycin, parathyroid hormone,desferrioxamine (DFO), or any combination thereof.
 22. A composition asdefined in claim 21, wherein said biologically active agent comprises aninterferon, interleukin-II, insulin, heparin, low molecular weightheparin, calcitonin, oxytosin, vasopressin, vancomycin, DFO, parathyroidhormone, and combinations thereof.
 23. A dosage unit form as defined inclaim 8, comprising a tablet, a capsule, or a liquid.
 24. A dosage unitform as defined in claim 23, wherein said dosing vehicle is selectedfrom the group consisting of water, 1,2-propane diol, ethanol, or anycombination thereof.
 25. A dosage unit form as defined in claim 13,comprising a tablet, a capsule, or a liquid.
 26. A dosage unit form asdefined in claim 25, wherein said dosing vehicle is selected from thegroup consisting of water, 1,2-propane diol, ethanol, or any combinationthereof.
 27. A dosage unit form as defined in claim 18, comprising atablet, a capsule, or a liquid.
 28. A dosage unit form as defined inclaim 27, wherein said dosing vehicle is selected from the groupconsisting of water, 1,2-propane diol, ethanol, or any combinationthereof.
 29. A method for administering a biologically-active agent toan animal in need of said agent, said method comprising administeringorally to said animal a composition as defined in claim
 2. 30. Acompound selected from the group consisting of

1 6-N-(3,5-dichloro-2-hydroxybenzoyl)aminocaproic acid

2 8(2-aminobenzoylamino)caprylic acid

3 8(2-trifluoromethoxy)benzoylamino caprylic acid

4 N-(2-hydroxybenzoyl)isonipecotic acid

5 4-[4-(2-aminobenzoylamino)phenyl]butyrylhydroxamic acid

6 4-(4-(pentafluorobenzoyl)aminophenyl)butyric acid

7 4-(4-(3-anisoyl)aminophenyl)butyric acid

8 8-(3-anisoyl)aminocaprylic acid

10 4-(4-(2-nitrobenzenesulfonyl)aminophenyl)butyric acid

11 8-(2-nitrobenzenesulfonyl)aminocaprylic acid

12 6-(4-(salicyloyl)aminophenyl)hexanoic acid

13 8-(2-methoxybenzoyl)amino caprylic acid

14 2-[4-Salicyloylamino)phenyl]ethyl methyl sulfone

15 1-Salicyloyl-2-succinyl hydrazide

16 3-(4-(2,5-dimethoxycinnamoyl)aminophenyl)propionic acid

17 4-(4-(2,5-dimethoxycinnamoyl)aminophenyl)butyric acid

18 1-salicyloyl-2-glutaryl hydrazide

19 Succinyl-4-aminosalicyclic acid

20 8-(Phenoxyacetylamino)caprylic acid

21 8-(2-pyrazinecarbonyl)aminocaprylic acid

22 4-(4-(2-pyrazinecarbonyl)aminophenyl)butyric acid

23 6-(4-(N-2-Nitrobenzoyl)aminophenyl)hexanoic acid

24 6-(4-(N-2-aminobenzoyl)aminophenyl)hexanoic acid

25 4-(4-(2-(3-carboxyl)pyrazinecarboxyl)aminophenyl)butyric acid

26 4(2-Nitrobenzoyl)aminophenylsuccinic acid

27 8-(2-(trifluoromethoxy)benzoyl)aminocaprylic acid

28

29 8-(Benzoylcarbonyl)caprylic acid

30 8-(phenylcarbonylamino)caprylic acid

31 2-[4-(2-Methoxybenzoylamino)phenyl]ethyl H₂PO₄

32 1-salicyloyl-2-suberyl hydrazide

33 4-(4-benzyloxycarbonylaminophenyl)butyric acid

34 4-(4-(2-hydroxynicotinoyl)aminophenyl)butyric acid

36 4-(4-phenyloxycarbonylaminophenyl)butyric acid

37 3-(2-methoxybenzoylamino)-1-propanol

38 8-(2-Hydroxynicotinoyl)aminocaprylic acid

39 6-(2-methoxybenzoyl)amino nicotinic acid

40 salicyloylglycine

41 4-(1-(2-pyrimidyl)piperazinoyl)butyric acid

42 8-(chromone-3-carbonyl)aminocaprylic acid

43 8-(vinylbenzoyl)aminocaprylic acid

44 4-(4-(chromone-3-carbonyl)aminophenyl)butyric acid

45 8-cinnamoylaminocapyrlic acid

46 5-(N-salicyloylamino)valeric acid

47 9-(2-hydroxybenzamido)nonanic acid

48 N-(4-salicyloylamino)-6-caproic acid

49 4′-flavonic acid

50 11-cinnamoylaminoundecanoic acid

51 4-octanoylamino-3-hydroxybenzoic acid

52 (3Phenyl2,3dihydroxypropanoyl)8aminocaprylic acid

53 8-[N-(3-coumarincarbonyl)]aminocaprylic acid

54 8-[N-(4-chlorobenzoyl)]aminocaprylic acid

55 8-[N-(3-fluorobenzoyl)]aminocaprylic acid

56 8-(N-2,5-Dihydroxybenzoyl)aminocaprylic acid

57 8-(N-2,3-Dimethoxybenzoyl)aminocaprylic acid

58 8-(N-2,4-Dihydroxybenzoyl)aminocaprylic acid

59 8-(N-2,5-Dimethoxybenzoyl)aminocaprylic acid

60 8-(N-3,5-Diacetyloxybenzoyl)aminocaprylic acid

61 8-(N-4-Hydroxybenzoyl)aminocaprylic acid (dimer)

62 8-(N-2,4-Dihydroxybenzoyl)aminocaprylic acid

63 10(N-2-Methoxyanilino)sebalic acid

65 2-Methoxybenzeneaminodecanoic acid

66 8-(N-benzoyl)aminocaprylic acid

68 8-[N-(4-fluorobenzoyl)aminocaprylic acid

69 8-[N-(3-bromobenzoyl)]aminocaprylic acid

70 8-(4-(1,2-dihydroxyethyl)benzoyl)aminocaprylic acid

71 8-[N-(4-bromobenzoyl)]aminocaprylic acid

72 8-[N-(4-iodobenzoyl)]aminocaprylic acid

73 4-{4-[N-(2-iodobenzoyl)aminophenyl]}butyric acid

74 4-{4-[N-(1-hydroxy-2-naphthoyl)aminophenyl]}butyric acid

75 4-(4-(2,4-dimethoxybenzoyl)aminophenyl)butyric acid

76 4-(o-anisoyl)aminophenylacetic acid

77 3-[4-(2,4-dimethoxybenzoyl)aminophenyl]propionic acid

78 4-{4-[N-(4-iodobenzoyl)]aminophenyl}butyric acid

80 4{4-[N-2-bromobenzoyl)]aminophenyl}butyric acid

81 4{4-[N-3-bromobenzoyl)aminophenyl}butyric acid

82 8-(N-3,5-Dihydroxybenzoyl)aminocaprylic acid

83 8-(N-3,5-Dimethoxy-4-hydroxybenzoyl)aminocaprylic acid

84 8-(N-2-6-Dimethoxybenzoyl)aminocaprylic acid

85 4-{4-[N-(4-bromobenzoyl)aminophenyl}butyric acid

86 8-(2-hydroxy-4-chlorobenzoyl)aminocaprylic acid

87 8-(N-2,6-Dihydroxybenzoyl)aminocaprylic acid

88 8-(N-2-Hydroxy6-methoxybenzoyl)aminocaprylic acid

89 8-(5-chloro-o-anisoyl)aminocaprylic acid

90 4-(4-(2,3-dimethoxybenzoyl)aminophenyl)butyric acid

91 4-(4-(5-chloro-o-anisoyl)aminophenyl)butyric acid

92 4-(4-(4-chloro-o-anisoyl)aminophenyl)butyric acid

93 8-(4-chloro-o-anisoyl)aminocaprylic acid

94 3-(4-(2,5-dimethoxybenzoyl)aminophenyl)propionic acid

95 4-{N-[4-(3-iodobenzoyl)aminophenyl}butyric acid

96 7-cinnamoylaminoheptanoic acid

97 8-N-(3-iodobenzoyl)aminocaprylic acid

98 8-N-(4-methoxy-3-nitrobenzoyl)aminocaprylic acid

99 8-N-(2-methoxy-4-nitrobenzoyl)aminocaprylic acid

100 4-{N-[4-(2-methoxy-4-nitrobenzoyl)aminophenyl}butyric acid

101 4-(4-(2,5-dimethoxybenzoyl)aminophenyl)butyric acid

104

105

106

107 4-(4-2,6-dimethoxybenzoyl)aminophenylbutyric acid

108 4-[4-N-(4-methoxy-3-nitrobenzoyl)aminophenyl]butyric acid

110 8-(N-2-hydroxy-5-iodobenzoyl)aminocaprylic acid

112 8-(N-2-hydroxy-4-nitrobenzoyl)aminocaprylic acid

113 4-[-N-(2-hydroxy-4-bromobenzoyl)aminophenyl]butyric acid

114 8-(N-2,3-Dihydroxybenzoyl)aminocaprylic acid

115 8-(N-3-methylsalicyloyl)aminocaprylic acid

116 8-(N-5-methylsalicyloyl)aminocaprylic acid

118 4-(4-(2-chloro-5-nitrobenzoyl)aminophenyl)butyric acid

119 4-{-[N-(2-hydroxy-5-iodobenzoyl)]aminophenyl}butyric acid

120 N-2-nitrophenyl-N′-(8-octanoic acid) urea

121 N-(2-methoxy-5-nitrophenyl) sebecoyl amide acid

123 8-[N-(2-acetoxy-3,5-dibromobenzoyl)]aminocaprylic acid

124 8-N-(2-chloro-6-fluorobenzoyl)aminocaprylic acid

125

126 8-N-(4-hydroxy-3-nitrobenzoyl)caprylic acid

127 4-(4-salicyloylaminophenyl)-4-oxobutyric acid

128 12-cinnamoyldodecanoic acid

129 4-{4-[N-(3-hydroxy-2-naphthoyl)aminophenyl]}butyric acid

130 8-(4-chloro-3-nitrobenzoyl)aminocaprylic acid

131 8-(2-chloronicotinoyl)aminocaprylic acid

132 8-(2-chloro-5-nitrobenzoyl)aminocaprylic acid

133 4-(4-phthalimidophenyl)butyric acid

134 4-{4-[N-(3-hydroxy-2-naphthoyl)aminophenyl}propanoic acid

135 3-(4-(2,6-dimethoxybenzoyl)aminophenyl)propionic acid

137 8-(N-2-chloro-4-fluorobenzoyl)aminocaprylic acid

138 8-(2-(1,2-dihydroisoindole-1-one))octanoic acid

139 8-(N-1-hydroxy-2-naphthoyl)aminocaprylic acid

140 8-(phthalimido)caprylic acid

142 6-(anisoyl)aminocaprylic acid

143 4-(4-(4-chloro-3-nitrobenzoyl)aminophenyl)butyric acid

144 11-N-(1-hydroxy-2-naphthoyl)aminoundecanoic acid

145 Bis(N-2carboxylphenyl-N-(N′-8-octanoic acid)urea)oxalyl diamide

146 2-[2-N-(2-chlorobenzoyl)aminoethoxy]ethanol

147 2-[2-N-(4-chlorobenzoyl)aminoethoxy]ethanol

148 4-(2-methoxybenzoyl)amino 3-carboxysufoxide

149 4-(2-methoxybenzoyl)amino 3-carboxypropylsulfone

150 4-(4-(3-hydroxyphthalimido)phenyl)butyric acid

151 2-[2-N-(2-methoxybenzoyl)aminoethoxy)]ethanol

152 2-[2-N-(3-chlorobenzoyl)aminoethoxy)]ethanol

153 Bis(N-2-carboxyphenyl-N-(N′-3(4-aminophenyl)propionicacid)ureal)oxaolyl diamide

154 trans-4-(2-aminobenzamidomethyl)cyclohexamecarboxylic acid

155 11-N-(3,5-dichloro-2-hydroxybenzoyl)aminoundecanoic acid

156 2-[N-(2-bromobenzoyl)aminoethoxy]ethanol

157 7-N-(3,5-dichloro-2-hydroxybenzoyl)aminoheptanoic acid

158 N-[3,5-dichloro-2-hydroxybenzoyl-4(4-aminophenyl)butyric acid

159 trans-4-(N-salicyoloylaminomethyl)cyclohexane carboxylic acid

160 N-[3,5-dichloro-2-hydroxybenzoyl-3-(4-aminophenyl)]propionic acid

161 12-N-(3,5-dichloro-2-hydroxybenzoyl)aminododecanoic acid

162 N-(2-hydroxy-4-carboxy)-6-heptanamide

163 N-(2-bromobenzoyl)morpholine

164 8-N-cyclohexanoylaminocaprylic acid

165 2-[N-(2-iodobenzoyl)aminoethoxy]ethanol

166 5-(4-chloro-2-hydroxyanilinocarbonyl)valeric acid

167 8-(2-hydroxyphenoxy)-aminocaprylic acid

168 N-Salicyloyl-5-(3-aminophenyl)valeric acid

169 4-(4-(2-ethoxybenzoyl)aminophenyl)butyric acid

170 9-[2-(3-hydroxy)pyridylaminocarbonyl]nonanic acid

171 7-(2-hydroxyphenoxyacetyl)aminocaprylic acid

172 2-[N-(2-hydroxybenzoylamino)ethoxy]ethanol

173 4-[N-(3,5-dichloro-2-hydroxybenzoyl)]aminophenylacetic acid

174 8-(2-hydroxy-5-chloroanilinocarbonyl)octanoic acid

175 N-salicyloyl-5-(4-aminophenyl)valeric acid

176 9-(2-hydroxy-5-methylanilinocarbonyl)nonanionic acid

177 5-(2-hydroxy-5-methylanilinocarbonyl)valeric acid

178 8-(pentafluorobenzoyl)aminocaprylic acid

179 3-(3-salicyloyl)aminophenyl)propionic acid

180 8-(2-ethoxybenzoyl)aminocaprylic acid

181 4-(4-(2-Dimethylaminobenzoic)aminophenyl)butyric acid

182 8-(3-Phenoxypropionylamino)caprylic acid

183 4-(Salicyloyl)aminophenylethyltetrazole

184 8(-(4(N-Salicyloyl-4aminophenyl)butyric)aminocaprylic acid [sic]

185 4-(4-(N-(2-Fluorocinnamoyl))aminophenyl)butyric

186 4-(4-(N-8(N-Salicyloyl)aminocaprylic)aminophenyl)butyric acid

187 8-(p-anisoyl)aminocaprylic acid

188 8-(4-Hydroxybenzoyl)aminocaprylic acid

189 8-(3-Hydroxybenzoyl)aminopcaprylic acid

190 8-(3,4,5-Trimethoxybenzoyl)aminocaprylic acid

191 8-(N-4-Methylsalicyloyl)aminocaprillic acid [sic]

192 N-10-(2-hydroxy-5-nitroanillino)decanoic acid

193 4-(4-(2-chloronicotinoyl)aminophenyl)butyric acid

and a salt of any of the foregoing.
 31. A method for preparing acomposition, said method comprising mixing: (A) at least one activeagent; (B) at least one compound as defined in claim 31; and (C)optionally, a dosing vehicle.